Modern Prodrug Design for Targeted Oral Drug Delivery

Arik Dahan; Zimmermann, Ellen M.; Ben-Shabat, Shimon
October 2014
Molecules;Oct2014, Vol. 19 Issue 10, p16489
Academic Journal
The molecular information that became available over the past two decades significantly influenced the field of drug design and delivery at large, and the prodrug approach in particular. While the traditional prodrug approach was aimed at altering various physiochemical parameters, e.g., lipophilicity and charge state, the modern approach to prodrug design considers molecular/cellular factors, e.g., membrane influx/efflux transporters and cellular protein expression and distribution. This novel targeted-prodrug approach is aimed to exploit carrier-mediated transport for enhanced intestinal permeability, as well as specific enzymes to promote activation of the prodrug and liberation of the free parent drug. The purpose of this article is to provide a concise overview of this modern prodrug approach, with useful successful examples for its utilization. In the past the prodrug approach used to be viewed as a last option strategy, after all other possible solutions were exhausted; nowadays this is no longer the case, and in fact, the prodrug approach should be considered already in the very earliest development stages. Indeed, the prodrug approach becomes more and more popular and successful. A mechanistic prodrug design that aims to allow intestinal permeability by specific transporters, as well as activation by specific enzymes, may greatly improve the prodrug efficiency, and allow for novel oral treatment options.


Related Articles

  • Prodrugs -- An Efficient Way to Breach Delivery and Targeting Barriers. Huttunen, Kristiina M.; Rautio, Jarkko // Current Topics in Medicinal Chemistry;Sep2011, Vol. 11 Issue 18, p2265 

    The study of prodrugs that are chemically modified bioreversible derivatives of active drug compounds to alter their undesired properties has been expanded widely during the last decades. Despite the commercial success the prodrugs have afforded, the concept is still quite unknown among many...

  • Synthesis and In Vitro Skin Permeation of Naproxen Conjugates with a- Alkylamino Acids. Pignatello, Rosario; Montenegro, Lucia; Stancampiano, Annalisa H. S.; Puelo, Antonina; Puglisi, Giovanni // Current Drug Delivery;Jun2005, Vol. 2 Issue 2, p185 

    Novel amide conjugates of the NSAID naproxen (NAP, 1) with short-chain a-alkylamino acids (C4 to C6 alkyl chain) were synthesized through a carbodiimide (EDAC)-assisted coupling reaction and evaluated as dermal prodrugs of NAP. The 2-a-aminobutyl derivative (2) showed lipophilicity similar to...

  • Design of Prodrugs to Enhance Colonic Absorption by Increasing Lipophilicity and Blocking Ionization. Nofsinger, Rebecca; Clas, Sophie-Dorothee; Sanchez, Rosa I.; Walji, Abbas; Manser, Kimberly; Nissley, Becky; Balsells, Jaume; Nair, Amrithraj; Qun Dang; Bennett, David Jonathan; Hafey, Michael; Junying Wang; Higgins, John; Templeton, Allen; Coleman, Paul; Grobler, Jay; Smith, Ronald; Yunhui Wu // Pharmaceuticals;Feb2014, Vol. 7 Issue 2, p207 

    Prodrugs are chemistry-enabled drug delivery modifications of active molecules designed to enhance their pharmacokinetic, pharmacodynamic and/or biopharmaceutical properties. Ideally, prodrugs are efficiently converted in vivo, through chemical or enzymatic transformations, to the active parent...

  • OPHTHALMIC MICROEMULSION: A COMPREHENSIVE REVIEW. MOHAN, KALE; PRAVIN, SURUSE; ATUL, BODHAKE // International Journal of Pharma & Bio Sciences;Jul-Sep2012, Vol. 3 Issue 3, p1 

    The design and development of new drug delivery systems with the intention of enhancing the efficacy of existing drugs is an ongoing process in pharmaceutical research. It is necessary for a pharmaceutical solution to contain a therapeutic dose of the drug in a volume convenient for...

  • Prodrug Design to Improve Pharmacokinetic and Drug Delivery Properties: Challenges to the Discovery Scientists. Jana, S.; Mandlekar, S.; Marathe, P. // Current Medicinal Chemistry;Nov2010, Vol. 17 Issue 32, p3874 

    No abstract available.

  • Self Micro-Emulsifying Drug Delivery System: Formulation Development and Biopharmaceutical Evaluation of Lipophilic Drugs. Patel, Deepa; Sawant, Krutika K. // Current Drug Delivery;Aug2009, Vol. 6 Issue 4, p419 

    No abstract available.

  • Recent Advances and Patents in Solid Dispersion Technology. Iqbal, Babar; Ali, Asgar; Ali, Javed; Baboota, Sanjula; Gupta, Sonal; Dang, Shweta; Muhammad, Shadab; Sahni, Jasjeet K. // Recent Patents on Drug Delivery & Formulation;Sep2011, Vol. 5 Issue 3, p244 

    High lipophilicity and high lattice energy of drugs, which result in poor solubility are major real challenges in the pharmaceutical industry for the successful development and commercialization of suitable dosage forms. Therefore various formulation strategies like complexation, lipid based...

  • Prediction of the Vitreal Half-Life of Small Molecular Drug-Like Compounds. Kidron, Heidi; Amo, Eva; Vellonen, Kati-Sisko; Urtti, Arto // Pharmaceutical Research;Dec2012, Vol. 29 Issue 12, p3302 

    Purpose: To build a fast, user-friendly computational model to predict the intravitreal half-lives of drug-like compounds. Methods: We used multivariate analysis to build intravitreal half-life models using two data sets, one with experimental data derived from both pigmented and albino rabbits...

  • Formulation Tactics for the Delivery of Poorly Soluble Drugs. Harikumar, S. L.; Aggarwal, Geeta // International Journal of PharmTech Research;Jul-Sep2012, Vol. 4 Issue 3, p914 

    As an upshot of modern drug discovery techniques like combinatorial chemistry research and inventive high throughput screening, number of new drug candidates developing, are often lipophilic. For poorly soluble drugs, a good bioavailability is typically needed to evaluate the therapeutic index...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics